拉帕替尼联合曲妥珠单抗治疗HER2阳性乳腺癌的疗效观察

Clinical observation of lapatinib combined with trastuzumab in treatment of HER2 positive breast cancer

目的探讨拉帕替尼联合曲妥珠单抗治疗HER2阳性乳腺癌患者的临床效果。方法选取2011年1月—2014年3月在宝鸡市妇幼保健院接受治疗的261例乳腺癌患者,随机分为拉帕替尼组(82例)、曲妥珠单抗组(84例)和联合组(95例),3组患者中途各有3、2和1例停止治疗。拉帕替尼组口服拉帕替尼片,6片/次,1次/d;曲妥珠单抗组静脉注射注射用曲妥珠单抗,1次/周,前9周4 mg/kg,后9周2 mg/kg维持;联合组治疗方法是上述两组治疗方法的联用,3组均连续治疗18周。治疗后,观察3组患者临床疗效,同时比较3组治疗前后无进展生存率(PFS)、总生存期(OS)、中枢神经系统(CNS)转移情况、总反应率(ORR)、临床受益反应(CBR)以及不良反应变化情况。结果治疗后,拉帕替尼组治愈率为21.52%,控制率为51.90%;曲妥珠单抗组治愈率为24.39%,控制率为57.32%;联合组治愈率为45.74%,控制率为76.60%,3组治愈率比较差异具有统计学意义(P<0.05),控制率比较差异具有统计学意义(P<0.01)。治疗后,拉帕替尼组、曲妥珠单抗组和联合组的PFS分别为41、43、55个月,联合组PFS比拉帕替尼组和曲妥珠单抗组均显著延长,差异具有统计学意义(P<0.05)。治疗后随访期间拉帕替尼组(72例)、曲妥珠单抗组(76例)和联合组(83例)的PFS分别为24、26、36个月,联合组的PFS比拉帕替尼组、曲妥珠单抗组的均显著延长,差异具有统计学意义(P<0.05)。治疗后,拉帕替尼组、曲妥珠单抗组和联合组的CNS转移率分别为32.91%、29.27%、19.15%,联合组的CNS转移率明显低于拉帕替尼组和曲妥珠单抗组,差异具有统计学意义(P<0.05)。拉帕替尼组、曲妥珠单抗组和联合组的ORR分别为56.96%、59.76%、76.60%,联合组ORR均高于拉帕替尼组、曲妥珠单抗组,差异具有统计学意义(P<0.05)。拉帕替尼组、曲妥珠单抗组和联合组的CBR分别为43.04%、47.56%、69.15%,联合组的均高于拉帕替尼组、曲妥珠单抗组,差异具有统计学意义(P<0.05)。联合组的不良反应发生率显著低于拉帕替尼组和曲妥珠单抗组,差异比较具有统计学意义(P<0.05)。结论拉帕替尼联合曲妥珠单抗对HER2阳性乳腺癌患者具有较好的临床治疗效果,具有一定的临床推广应用价值。

Objective To observe the therapeutic effect of lapatinib combined with trastuzumab in treatment of HER2 positive breast cancer. Methods Patients （261 cases） with breast cancer in Baoji Maternal and Child Health Hospital from January 2011 to March 2014 were randomly divided into lapatinib group （82 cases）, trastuzumab group （84 cases）, and combination group （95 cases）, and there were respectively 3, 2 and, 1 patients discontinuing treatment. Patients in the lapatinib group were po administered with Lapatinib Tablets, 6 tablets/time, once daily. Patients in the trastuzumab group were iv administered with Trastuzumab for injection, once a week, the dosage in the first 9 weeks was 4 mg/kg, and 2 mg/kg for the last 9 weeks, The treatment method in the combination group was the combination of the lapatinib and trastuzumab groups. Patients in three groups were treated for 18 weeks. After treatment, the clinical efficacy was evaluated, and PFS, OS, the transfer situation of CNS, ORR, CBR and adverse reactions in three groups before and aider treatment were compared. Results After treatment, the cure and control rate in the lapatinib group respectively were 21.52% and 51.90%, which in the trastuzumab group were 24.39% and 57.32%, and were 45.74% and 76.60% in the combination group, the difference of cure rate among three groups was statistically significant （P 〈 0.05）, and the difference of control rate among three groups was statistically significant （P 〈 0.01）. After treatment, PFS in the lapatinib, tmstuzumab, and combination groups respectively were 41, 43, and 55 months, PFS in the combination group was significantlylonger than that in the other groups with significant difference （P 〈 0.05）. After treatment, CNS transfer rate in the lapatinib, trastuzumab, and combination group respectively were 32.91%, 29.27%, and 19.15%, and CNS transfer rate in the combination group was significantly lower than that in the other groups with significant difference （P 〈 0.05）. After treatment, ORR in the lapatinib, trastuzumab, and combination group respectively were 56.96%, 59.76%, and 76.60%, and ORR in the combination group was significantly higher than that in the other groups with significant difference （P 〈 0.05）. After treatment, CBR in the lapatinib, trastuzumab, and combination group respectively were 43.04%, 47.56%, and 69.15%, and CBR in the combination group was significantly higher than that in the other groups with significant difference （P 〈 0.05）. The incidence of adverse reactions in the combination group was significantly lower than the other groups with significant difference （P 〈 0.05）. Conclusion Lapatinib combined with trastuzumab has a significant clinical therapeutic effect in treatment of HER2 positive breast cancer, which has a certain clinical application value.